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Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02130
Both isoproterenol and tidal
fluctuations of muscle length inhibit active force development in
activated airway smooth muscle. In this study, we show that length
fluctuations in the range of amplitudes expected during quiet tidal
breathing produce force inhibition that is equipotent with high
concentrations of isoproterenol. Active force fell to 50% of its
isometric value when the amplitude of the tidal stretch was 4% of
muscle length. The relaxing effects of length fluctuations were
insensitive to the specific contractile agonist, suggesting that the
mechanism of action is largely independent of the particular signal
transduction pathway and lies instead at the level of bridge dynamics.
This idea is reinforced by the results of combining the relaxation
effects of tidal fluctuations with those produced by isoproterenol at
all but the highest concentrations studied (10
5 M). Such
a combination produces multiplicative effects, indicating largely separate modes of action. These observations suggest that the
tidal muscle stretches that are attendant to spontaneous breathing comprise the first line of defense against bronchospasm and that tidal
muscle stretches may be the most important of all known bronchodilating agencies.
bronchodilating agents; 
-agonists; bronchospasm
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